A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: molecular and computational evidence
| Autor: | Katerina Hatzi, Carol Moreno, C. Belessi, Paolo Ghia, Frederic Davi, Richard Rosenquist, Pär Josefsson, Nicholas Chiorazzi, Fiona Murray, Kostas Stamatopoulos, Achilles Anagnostopoulos, Nikolaos Laoutaris, J. Jurlander, A. Hadzidimitriou, Athanasios Tsaftaris, Nikos Darzentas |
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| Přispěvatelé: | Darzentas, N, Hadzidimitriou, A, Murray, F, Hatzi, K, Josefsson, P, Laoutaris, N, Moreno, C, Anagnostopoulos, A, Jurlander, J, Tsaftaris, A, Chiorazzi, N., Belessi, C., Ghia, PAOLO PROSPERO, Rosenquist, R, Davi, F, Stamatopoulos K. Ghia P., is the corresponding author |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Chronic lymphocytic leukemia Molecular Sequence Data B-cell receptor Immunoglobulin Variable Region Receptors Antigen B-Cell Biology Mice Immune system Antigen hemic and lymphatic diseases medicine Animals Humans Amino Acid Sequence Phylogeny Genetics Innate immune system breakpoint cluster region Hematology medicine.disease Complementarity Determining Regions Leukemia Lymphocytic Chronic B-Cell B-1 cell Stereotypy (non-human) Oncology Immunology Immunoglobulin Heavy Chains |
| Zdroj: | Leukemia. 24:125-132 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | Chronic lymphocytic leukemia (CLL) is uniquely characterized by the existence of subsets of cases with quasi-identical, 'stereotyped' B-cell receptors (BCRs). Herein we investigate this stereotypy in 2662 patients with CLL, the largest series yet, using purpose-built bioinformatics methods based on sequence pattern discovery. Besides improving the identification of 'stereotyped' cases, we demonstrate that CLL actually consists of two different categories, based on the BCR repertoire, with important biological and ontogenetic differences. The first (similar to 30% of cases) shows a very restricted repertoire and is characterized by BCR stereotypy (clustered cases), whereas the second includes cases with heterogeneous BCRs (nonclustered cases). Eleven major CLL clusters were identified with antigen-binding sites defined by just a few critically positioned residues, regardless of the actual immunoglobulin (IG) variable gene used. This situation is closely reminiscent of the receptors expressed by cells participating in innate immune responses. On these grounds, we argue that whereas CLL cases with heterogeneous BCRs likely derive from the conventional B-cell pool, cases with stereotyped BCRs could derive from progenitor cells evolutionarily adapted to particular antigenic challenges, perhaps intermediate between a true innate immune system and the conventional adaptive B-cell immune system, functionally similar to what has been suggested previously for mouse B1 cells. Leukemia (2010) 24, 125-132; doi:10.1038/leu.2009.186; published online 17 September 2009 |
| Databáze: | OpenAIRE |
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